(7a) Multifunctional DNA Nanostructures for Therapeutic Delivery

DNA nanostructures offer several advantages over conventional therapeutic carriers such as liposomes and polymeric particles, including biocompatibility, biodegradability, and low immunogenicity. Furthermore,  a simple one-pot self-assembly fabrication process results in nearly monodisperse particle sizes with controllable spatial location of ligands.  We have previously shown that these DNA nanostructures are resistant to nuclease degradation and can be used to deliver antisense DNA to cells. However, these first-generation carriers lacked target specificity and demonstrated limited cell uptake.

In this work, self-assembled DNA tetrahedron nanostructures bearing multivalent DNA aptamers are shown to selectively target HeLa cancer cells and trigger efficient intracellular uptake, as determined by flow cytometry.  The improved uptake relative to naked DNA nanostructures and linear DNA relies on aptamer multivalency and is concentration-dependent.  In addition, the specific aptamer used in this work has therapeutic activity of its own: it is known to cause the down-regulation of Bcl-2, a protein regulator of apoptosis.

We are currently exploring strategies to induce cancer cell apoptosis through combined antisense and aptamer delivery via DNA tetrahedrons.  Our in vitro results demonstrate a synergistic effect due to antisense and aptamer co-delivery and suggest that multifunctional DNA nanostructures could have great potential as therapeutic delivery vehicles.